Despite extensive large population analysis, genome-wide association studies of diseases with single nucleotide polymorphisms (SNPs) have been disappointing thus far because SNPs account for a small fraction of the genetic risk for disease. We hypothesize that rare genetic variants giving rise to functional mutations may account for susceptibility to certain rheumatic illnesses. Moreover, we propose a strategy to further accelerate decreases in costs of exome sequencing by establishing a high throughput platform to enrich analysis of immune related genes. These sequences will then be analyzed for potential disease causing mutations by computational approaches.